miR-26a enhances colorectal cancer cell growth by targeting RREB1 deacetylation to activate AKT-mediated glycolysis.

We previously reported the inhibitory effects of microRNA-26a (miR-26a) on the conversion of pyruvate to acetyl coenzyme A in glucose metabolism by directly targeting pyruvate dehydrogenase protein X component in colorectal cancer (CRC) cells (Chen B et al., BMC Cancer 2014). Here, using microRNA in situ hybridization, we confirmed that miR-26a levels were elevated in 77 human CRC tissue samples and further investigated the key miR-26a-mediated metabolic regulation elements and signaling pathways in CRC cells through quantitative proteomic dissection combined with cancer cell biology and biochemical loss-of-function analysis. We found that AKT transcription signaling was a target pathway via miR-26a-mediated deacetylation modification of Ras-responsive element-binding protein 1 (RREB1) at the Lys-60 residue. miR-26a improved the deacetylation level of RREB1, thus contributing to RREB1 binding to the AKT1 promoter to activate AKT transcription and its related signaling pathway in glycolysis. Moreover, miR-26a promoted CRC tumorigenesis in CRC cells and subcutaneous xenograft mice. Thus, miR-26a is a key regulator of CRC tumorigenesis that mediates the deacetylation modification of RREB1 to enhance AKT1 transcription and downstream target gene expression in glycolysis for CRC growth.

Relationship Between Medication Adherence and Distance to Dispensing Pharmacies and Prescribers Among an Urban Medicaid Population with Diabetes Mellitus.

STUDY OBJECTIVE: To determine whether a relationship exists between medication adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and distance to dispensing pharmacies and prescribers among an urban public aid population with diabetes mellitus. DESIGN: Retrospective cohort study using claims data. DATA SOURCE: Illinois Department of Healthcare and Family Services database. PATIENTS: A total of 6532 patients aged 18-64 years with diabetes who had at least one prescription fill for an ACEI or ARB and had continuous Medicaid coverage in the greater Chicago area in 2009. MEASUREMENTS AND MAIN RESULTS: We assessed medication adherence, defined as proportion of days covered (PDC) of 0.8 or higher, to ACEIs and ARBs and its association with distances between patients and their pharmacies and prescribers. Of the 6532 patients included in the analyses, 2930 (45%) had PDC levels of 0.8 or higher. No significant differences were observed between patients who were adherent versus those who were nonadherent in distance to pharmacy (median 1.39 vs 1.35 miles, p=0.15) or distance to prescriber (median 4.39 vs 4.48 miles, p=0.80). In a multivariate regression model including age, sex, race/ethnicity, number of pharmacies, number of prescribers, distance to pharmacy, and distance to prescriber, a greater number of prescribers was associated with higher adherence (two prescribers vs one prescriber: odds ratio [OR] 1.396, 95% confidence interval [CI] 1.233-1.580; three or more prescribers vs one prescriber: OR 2.208, 95% CI 1.787-2.727). CONCLUSION: ACEI or ARB adherence was not associated with distances to pharmacies and prescribers.

Traveling towards disease: transportation barriers to health care access.

Transportation barriers are often cited as barriers to healthcare access. Transportation barriers lead to rescheduled or missed appointments, delayed care, and missed or delayed medication use. These consequences may lead to poorer management of chronic illness and thus poorer health outcomes. However, the significance of these barriers is uncertain based on existing literature due to wide variability in both study populations and transportation barrier measures. The authors sought to synthesize the literature on the prevalence of transportation barriers to health care access. A systematic literature search of peer-reviewed studies on transportation barriers to healthcare access was performed. Inclusion criteria were as follows: (1) study addressed access barriers for ongoing primary care or chronic disease care; (2) study included assessment of transportation barriers; and (3) study was completed in the United States. In total, 61 studies were reviewed. Overall, the evidence supports that transportation barriers are an important barrier to healthcare access, particularly for those with lower incomes or the under/uninsured. Additional research needs to (1) clarify which aspects of transportation limit health care access (2) measure the impact of transportation barriers on clinically meaningful outcomes and (3) measure the impact of transportation barrier interventions and transportation policy changes.

Severe postvaccinia encephalitis with acute disseminated encephalomyelitis: recovery with early intravenous immunoglobulin, high-dose steroids, and vaccinia immunoglobulin.

We report the second case of severe postvaccinial encephalitis with acute disseminated encephalomyelitis since smallpox vaccination was reintroduced in 2002. Both affected patients responded dramatically with early intervention of intravenous immunoglobulin. Our patient, who also received concurrent vaccinia immunoglobulin and corticosteroids, demonstrated full recovery.